Abstract
purpose. To test the hypothesis that eyes with amblyopia may have thicker retina, retinal nerve fiber layer thickness (RNFLT) was investigated in patients with unilateral amblyopia.
methods. Thirty-eight patients with unilateral amblyopia were studied. Among them, 20 patients had amblyopia with strabismus and 18 had refractive amblyopia without strabismus. Nineteen of 38 had anisometropia of 2.0 D or more. In addition, 17 patients with anisometropia of 2.0 D or more but without amblyopia were enrolled as control subjects. RNFLT was measured by optical coherence tomography with scan pattern “Nerve Head 2.0R” (Carl Zeiss Meditec, Dublin, CA). Average RNFLT was multiplied with their corresponding scan circumferences to estimate the integral values of the total RNFL area (RNFLTestimated integrals).
results. In all 38 patients with unilateral amblyopia, the difference in RNFLT and in RNFLTestimated integrals between the amblyopic eyes and the normal fellow eyes were statistically significant. Multivariate regression analysis with adjustment for axial length, spherical equivalence, age, and sex indicated significant differences as well. In the group of strabismic amblyopia, the difference in RNFLT and in RNFLTestimated integrals between the amblyopic eyes and the normal fellow eyes did not reach statistical significance. However, in the group of refractive amblyopia, the difference in RNFLT and in RNFLTestimated integrals between the amblyopia eyes and the normal fellow eyes both had a statistical significance. In the 19 patients with anisometropic amblyopia, the difference in RNFLT and in RNFLTestimated integrals between the amblyopic eyes and the normal fellow eyes were statistically significant. In the control group of 17 patients with nonamblyopic anisometropia, the difference in RNFLT and in RNFLTestimated integrals between both eyes did not reach statistical significance.
conclusions. RNFLT may be affected by refractive amblyopia, but further histopathologic confirmation is needed.
Amblyopia is considered to be a developmental disorder of spatial vision that is associated with the presence of strabismus, anisometropia, or form deprivation early in life.
1 If the same disorders occur later in life, amblyopia does not develop.
The amblyopic process may have an effect on various levels of the visual pathway. Shrinkage of cells in the lateral geniculate nucleus that receive input from the amblyopic eye
2 3 4 5 6 7 and a shift in the dominance pattern in the visual cortex
8 9 10 11 12 have been reported. Retinal involvement accompanying amblyopia is controversial.
13 14 15 16 17
During fetal development, there is a rapid decline in cell density in the retinal ganglion cell layer toward the end of gestation. In humans, the total population of cells in the ganglion cell layer is highest (2.2–2.5 million cells) between approximately weeks 18 and 30 of gestation. After this, the cell population declines rapidly to 1.5 to 1.7 million cells.
18 The number of axons in the human optic nerve also decreases during gestation.
19 At 16 to 17 weeks of gestation, the estimated number of axons was 3.7 million. The number of axons in the human adult optic nerve is 1.1 million. In rat retina, the number of retinal ganglion cells projecting to the central visual nuclei is reduced by at least 35%, and the process ceases by 2 weeks postnatally.
20 If amblyopia affects the process of postnatal reduction of ganglion cells, RNFL thickness may be thicker than that in the normal eye. It was our plan to investigate retinal nerve fiber layer thickness (RNFLT) in amblyopic eyes to determine whether it is thicker.
Several techniques to evaluate the RNFLT, such as red-free ophthalmoscopy, scanning laser polarimetry (SLP) and optical coherence tomography (OCT) have been described. SLP estimates RNFLT based on the retardation of the laser beam caused by the birefringence of the RNFL. Because the cornea is also birefringent, erroneous RNFLT assessment can be made without proper anterior segment compensation.
21 22 23 OCT is a noninvasive, noncontact technique that measures RNFLT.
24 25 The RNFLT measured by OCT corresponds to the RNFLT measured histologically.
24 Because OCT is based on near-infrared interferometry, the thickness measurement is not affected by refractive status or axial length of the eye, nor by light changes in nuclear sclerotic cataract density.
26 RNFLT remains unchanged after laser-assisted in situ keratomileusis (LASIK).
27 Posterior subcapsular and cortical cataracts, heavy nuclear cataracts, secondary cataracts, loss of vitreous body transparency, and silicone oil in the vitreous chamber, however, reduce the ability to perform OCT.
26 28 Excluding these conditions, OCT is a reliable imaging technology. The purpose of our investigation was to use OCT to measure RNFLT in patients with unilateral amblyopia, to see whether the RNFL is thicker in the amblyopic eye.
Approval for this project was obtained from the institutional review board of Taipei Veterans General Hospital. The study was performed according to the tenets of the Declaration of Helsinki for research involving human subjects. Patients with unilateral amblyopia were consecutively enrolled. Clinical examinations included best corrected visual acuity, refraction error, slit lamp examination, extraocular movements, intraocular pressure, fundoscopy, and A-scan for axial length. Patients with organic eye disease, a history or evidence of intraocular surgery, history of cataract, glaucoma, retinal disorders, or laser treatment and children not cooperative enough for OCT examination were excluded.
A total of 38 patients with unilateral amblyopia were enrolled. Twenty had strabismic amblyopia
(Table 1) . The other 18 without strabismus had a diagnosis of refractive amblyopia
(Table 2) . Of the 38 patients with unilateral amblyopia, 19 also had anisometropia, including 7 from the group with strabismic amblyopia and 12 from the group with refractive amblyopia
(Table 3) . Anisometropia was defined as a difference in spherical equivalence of 2.0 D or more between the two eyes. For the purpose of comparison, in addition, 17 patents with nonamblyopic anisometropia were enrolled as control subjects
(Table 4) .
Among 38 patients with unilateral amblyopia, 23 were male and 15 were female. The mean ± SD age was 26.4 ± 18.3 years. The eye with amblyopia was the right eye in 19 patients and the left eye in 19 patients. Best corrected vision of the amblyopic eye ranged from 20/1200 to 20/30. Best corrected vision of the normal eye was equal to or better than 20/20. The mean age of 20 patients with strabismic amblyopia was 27.4 ± 18.6 years, and the mean age of 18 patients with refractive amblyopia was 25.4 ± 18.6 years. The mean age of 17 normal control subjects was 28.5 ± 12.2 years.
In all 38 patients with unilateral amblyopia, the difference in RNFLT between the amblyopic eyes and the normal fellow eyes was statistically significant
(Table 5) . The difference in RNFLT
estimated integrals between the amblyopic eyes and the normal fellow eyes was also statistically significant
(Table 6) . Multivariate regression analysis with adjustment for axial length, spherical equivalence, age, and sex indicated a significant difference in RNFLT and in RNFLT
estimated integrals as well. Although the spherical equivalence in amblyopic eyes (0.17 ± 3.59 D) was higher than that in normal fellow eyes (−0.81 ± 2.33 D), the difference was not statistically significant (
P = 0.084). In addition, there was no significant correlation between RNFLT and axial length (ρ = −0.075,
P = 0.655) or spherical equivalence (ρ = −0.009,
P = 0.956) among all amblyopic eyes. RNFLT in all amblyopic eyes did not correlate with logMAR visual acuity (
P = 0.104) after adjustment for age.
Further analysis was performed separately for strabismic and refractive amblyopia. In the group with strabismic amblyopia, the difference in RNFLT and RNFLT
estimated integrals between the amblyopic eyes and the normal fellow eyes did not reach statistical significance. However, in the group of refractive amblyopia, the difference in RNFLT and in RNFLT
estimated integrals between the amblyopic eyes and the normal fellow eyes were statistically significant
(Tables 5 6) .
In the 19 patients with anisometropic amblyopia, the difference between RNFLT and RNFLT
estimated integrals in the amblyopic eyes and in the normal fellow eyes both were statistically significant
(Tables 5 6) . The differences were significant in the multivariate regression analysis as well. In the control group of 17 patients with nonamblyopic anisometropia, the difference in RNFLT and in RNFLT
estimated integrals between the two eyes both did not reach statistical significance
(Tables 7 8) .
Difference in RNFL thickness may come from glaucomatous damage and subjects older than 40 may confound the data analysis. Therefore, we also analyzed the data excluding subjects older than 40. The number of subjects was reduced to 31 from 38 (amblyopic) and to 13 from 17 (control). With a sample size of 31, the study had more than 80% statistical power to detect a 6% increase in RNFL thickness in amblyopic eyes, compared with the normal eyes. The results of RNFLT and RNFLTestimated integrals of the reduced number also consisted with the results of total number.